Objective Colorectal cancer survival has been linked to the microbiome. Single organism analyses suggest Fusobacterium nucleatum as a marker of poor prognosis. However, in situ imaging of tumors demonstrate a polymicrobial tumor-associated community. To understand the role of these polymicrobial communities in survival, we performed an untargeted study of the microbiome in late-stage colorectal cancer patients. Design We conducted a nested case-control study in late-stage cancer patients undergoing resection for primary adenocarcinoma. The microbiome of paired colorectal tumor and adjacent tissue samples was profiled using 16S rRNA sequencing; we used compositionally aware ordination and differential ranking to profile the microbial community. Results. We found a consistent difference in the microbiome between paired tumor and adjacent tissue, despite strong individual microbial identities. Tumors had higher relative abundance of genus Fusobacteria and Campylobacter at the expense of members of families Lachnospriaceae and Rumminococeae. Furthermore, a larger difference between normal and tumor tissue was associated with prognosis: patients with shorter survival had a larger difference between normal and tumor tissue. We found the difference was specifically related to taxa previously associated with cancer. Within the tumor tissue, we identified a 39 member community statistic associated with survival; for every log2 fold increase in this value, an individual's odds of survival increased by 20% (OR survival 1.20; 95% CI 1.04, 1.33). Conclusion Our results suggest that a polymicrobial tumor-specific microbiome is associated with survival in late-stage colorectal cancer patients.

The authors have declared no competing interest.

This work was funded by Futurum-Academy for Healthcare, Region Jönköping County, Sweden (grant FUTURUM-933436 and FUTURUM-809281), as well as centre grant from Ferring Pharmaceuticals for the establishment of the Centre for Translational Microbiome Research. JTM was funded by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The funders were not involved in the development, analysis, or interpretation of the study.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Regional Ethical Review Board in Linkpöing, Linköping, Sweden gave ethical approval for this work. (Application 98113, 2013/271-31)

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors